Renine is an enzyme which is synthesized and released from specialized cells in the wall of the afferent arteriole at the juxtaglomerular apparatus. Release of renin appears to be the major controlling step in generation of the potent vasoconstrictor and aldosterone secretagogue angiotensin II. There is evidence that abnormalities in control of renin secretion may play a role in certain forms of hypertension and perhaps in other disease states. Arterial pressure and tubular fluid composition at the adjacent macula densa are generally believed to be the two major physiological variables which control the rate of renin secretion. The present investigation aims to clarify the cellular mechanisms for these control processes. Proposed studies utilize a newly developed approach which applies isolated perfused tubule methods to the microdissected juxtaglomerular apparatus. With this method, the tubule segment containing the macula densa can be perfused, fluid composition at the macula densa manipulated, and the response of single JGA renin secretion measured. We propose to use this technique to determine the role of prostaglandins, adenosine, and local intertitial osmolarity in the macula densa mechanism for control of renin secretion. In other studies, the afferent arteriole is cannulated and arteriolar stretch varied, permitting study of the mechanisms underlying the pressure sensitivity of renin release. We plan to evaluate the role of stretch-dependent activation of calcium channels and the endothelium in pressure-sensitive renin release. These new in vitro methods offer substantial advantage over classic methods for study of the baroreceptor and macula densa mechanisms. Agonist and antagonist studies are facilitated by direct access to tubular, intravascular and interstitial compartments. Direct visualization and access to individual cells permit use of optical and electrophysiological methods.